Abstract
Atherosclerosis (ATS), the change in structure and function of arteries with associated lesion formation and altered blood flow, is the leading cause of cardiovascular disease, the number one killer worldwide. Beyond dyslipidemia, chronic inflammation, together with aberrant phenotype and function of cells of both the innate and adaptive immune system, are now recognized as relevant contributors to atherosclerosis onset and progression. While the role of macrophages and T cells in atherosclerosis has been addressed in several studies, Natural Killer cells (NKs) represent a poorly explored immune cell type, that deserves attention, due to NKs’ emerging contribution to vascular homeostasis. Furthermore, the possibility to re-polarize the immune system has emerged as a relevant tool to design new therapies, with some succesfull exmples in the field of cancer immunotherapy. Thus, a deeper knowledge of NK cell pathophysiology in the context of atherosclerosis and atherosclerosis-associated risk factors could help developing new preventive and treatment strategies, and decipher the complex scenario/history from “the risk factors for atherosclerosis” Here, we review the current knowledge about NK cell phenotype and activities in atherosclerosis and selected atherosclerosis risk factors, namely type-2 diabetes and obesity, and discuss the related NK-cell oriented environmental signals.
Highlights
Cardiovascular diseases (CVDs), the first cause of death worldwide, are characterized by an inflammatory microenvironment [1,2,3]
It has been reported that within visceral adipose tissue (VAT) of mice receiving high-fat diet (HFD), natural killer (NK) cells support the development of obesityinduced insulin resistance, via induction of pro-inflammatory/ M1-like macrophages, through a mechanism mediated by NKderived cytokines, including TumorNecrosis Factor-a (TNFa) [121] (Figure 2E)
Inflammation is a common hallmark of CVDs, including ATS and ATS-associated risk factors, such as obesity, and Type 2 Diabetes (T2D)
Summary
Cardiovascular diseases (CVDs), the first cause of death worldwide, are characterized by an inflammatory microenvironment [1,2,3]. EC dysfunction in ATS leads to proinflammatory cytokines production and immune cells recruitment within the atherosclerotic plaque [9] This tight connection between inflammation and CVDs has been recently reinforced by the results of two clinical trials (Canakinumab Anti-inflammatory Thrombosis Outcomes Study-CANTOS, and Low Dose Colchicine for Secondary Prevention of Cardiovascular Disease-LoDoCo) that show the benefit of targeting inflammation to lower the risk of CV events [10, 11]. Immune cells, both of innate and adaptive immunity, are characterized by extraordinary plasticity, they can adapt their phenotype and response (referred as immune cell polarization) to the hosting pathophysiological micro-(tissue/local) and macro-(peripheral blood/systemic) environment [14,15,16,17,18,19] These adaptation capabilities result in the ability of immune cells to acquire contrasting activities, as related to their “original commitment”, which is the defense of the host organism. We review the current knowledge of NK cell phenotype and activities, discussing the environmental cues that can instruct NK cell behavior in ATS pathological context
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